Norms on the gender perception of role nouns in Czech, English, French, German, Italian, Norwegian, and Slovak

We collected norms on the gender stereotypicality of an extensive list of role nouns in Czech, English, French, German, Italian, Norwegian, and Slovak, to be used as a basis for the selection of stimulus materials in future studies. We present a Web-based tool (available at https://www.unifr.ch/lcg/) that we developed to collect these norms and that we expect to be useful for other researchers, as well. In essence, we provide (a) gender stereotypicality norms across a number of languages and (b) a tool to facilitate cross-language as well as cross-cultural comparisons when researchers are interested in the investigation of the impact of stereotypicality on the processing of role nouns.

Bongars Quellenwerk zur Geschichte der Kreuzzüge

ln seinen letzten Lebensjahren gab Jacques Bongars (1554-1612) unter dem Titel Gesta Dei per Francos (Gottes Taten durch die Franken) eine zweibändige Sammlung von mittelalterlichen Texten zu den Kreuzzügen heraus, die 1611 im Verlagshaus Wechel in Hanau erschien. Er stellte in seinem Quellenwerk gegen zwanzig Texte verschiedenster Autoren zusammen, von denen viele zum ersten Mal überhaupt gedruckt wurden. Der zweite Band enthält ausschliesslich die Geschichte der Kreuzzüge des Venezianers Marino Sanudo d. Ä. (ca. 1270-ca. 1343). Diese Schrift mit dem Titel Liber secretorum fidelium crucis ist wissenschaftsgeschichtlich bedeutend aufgrund der darin enthaltenen Karten: einer Weltkarte, einer Karte von Ägypten (bzw. des östlichen Mittelmeeres und des Roten Meeres), einer Karte des Heiligen Landes sowie der Stadtpläne von Akkon und Jerusalem.

John Garstang at Sirkeli Höyük, Cilician Plain, in 1936-1937: Old Photographs and New Evidence from the Renewed Excavations

During the winter of 1936-1937, British archaeologist John Garstang (1876-1956) excavated several trenches at the site of Sirkeli Höyük, located in the Plain of Cilicia (18 km west of modern-day Ceyhan). After a single campaign, however, he left the site and his interest shifted to site of Yumuktepe/Mersin, where he then excavated for a number of years. Apart from two very brief preliminary reports of his excavations at Sirkeli Höyük, which were published in the journal 'Annals of Archaeology and Anthropology of the University of Liverpool', not much is known about the trenches and their associated finds. Unpublished photographs kept in the Special Archives of University College London shed new light on the location and orientation of some of Garstang’s trenches at the site. Furthermore, in the 2012 campaign of the renewed Turkish-Swiss excavations at the site, a trench was found in the western part of the northern terrace that most probably was excavated by Garstang, but was not mentioned by him in his reports. This hitherto unknown trench may be related to his discovery of a lion-shaped column base made of basalt that is now kept in the collections of the Archaeological Museum of Adana.

Dermatopathology in sub-Saharan Africa: a systematic 5-year analysis of all histopathological diagnoses from the Regional Dermatology Training Centre (RDTC) in Moshi, Tanzania.

BACKGROUND Proper diagnosis of skin diseases relies on dermatopathology, the most important diagnostic technique in dermatology. Unfortunately, there are few dermatopathology institutions in sub-Saharan Africa, where little is known about the spectrum of histopathological features observed. OBJECTIVES To investigate the spectrum of dermatopathological diagnoses made in a sub-Saharan African reference centre of a large, mainly rural area. PATIENTS/METHODS To retrospectively evaluate all dermatopathological diagnoses made over a period of 5 years at the Regional Dermatology Training Centre (RDTC) in Moshi, Tanzania. RESULTS There were a total of 1554 skin biopsy specimens. In 45% of cases, there were inflammatory diseases, most frequently lichenoid conditions. Cutaneous neoplasms represented 30.4% of all diagnoses, with Kaposi's sarcoma (KS) and, less frequently, squamous cell carcinoma (SCC) being the two most common neoplastic conditions. The latter also reflected the intensive management of persons with albinism in the RDTC. The distribution of histological diagnoses seemed to correlate with the overall clinical spectrum of cutaneous diseases managed in the RDTC. CONCLUSIONS In this African study inflammatory conditions are the main burden of skin diseases leading to a diagnostic biopsy. Our findings provide further evidence that KS, primarily related to the high prevalence of HIV infection is an epidemiological problem. Both SCC and basal cell carcinoma represent another relatively common malignant cutaneous neoplasms, reflecting the presence of specific populations at risk. The challenging spectrum of histological diagnoses observed in this specific African setting with basic working conditions shows that development of laboratory services of good standards and specific training in dermatopathology are urgently needed.

Relative positioning of classical benzodiazepines to the γ2-subunit of GABAA receptors.

GABAA receptors are the major inhibitory neurotransmitter receptors in the brain. Benzodiazepine exert their action via a high affinity-binding site at the α/γ subunit interface on some of these receptors. Diazepam has sedative, hypnotic, anxiolytic, muscle relaxant, and anticonvulsant effects. It acts by potentiating the current evoked by the agonist GABA. Understanding specific interaction of benzodiazepines in the binding pocket of different GABAA receptor isoforms might help to separate these divergent effects. As a first step, we characterized the interaction between diazepam and the major GABAA receptor isoform α1β2γ2. We mutated several amino acid residues on the γ2-subunit assumed to be located near or in the benzodiazepine binding pocket individually to cysteine and studied the interaction with three ligands that are modified with a cysteine-reactive isothiocyanate group (-NCS). When the reactive NCS group is in apposition to the cysteine residue this leads to a covalent reaction. In this way, three amino acid residues, γ2Tyr58, γ2Asn60, and γ2Val190 were located relative to classical benzodiazepines in their binding pocket on GABAA receptors.

Accelerated discovery of novel benzodiazepine ligands by experiment-guided virtual screening.

High throughput discovery of ligand scaffolds for target proteins can accelerate development of leads and drug candidates enormously. Here we describe an innovative workflow for the discovery of high affinity ligands for the benzodiazepine-binding site on the so far not crystallized mammalian GABAA receptors. The procedure includes chemical biology techniques that may be generally applied to other proteins. Prerequisites are a ligand that can be chemically modified with cysteine-reactive groups, knowledge of amino acid residues contributing to the drug-binding pocket, and crystal structures either of proteins homologous to the target protein or, better, of the target itself. Part of the protocol is virtual screening that without additional rounds of optimization in many cases results only in low affinity ligands, even when a target protein has been crystallized. Here we show how the integration of functional data into structure-based screening dramatically improves the performance of the virtual screening. Thus, lead compounds with 14 different scaffolds were identified on the basis of an updated structural model of the diazepam-bound state of the GABAA receptor. Some of these compounds show considerable preference for the α3β2γ2 GABAA receptor subtype.

Magie de la comparaison. Et autres études d’histoire des religions

Jonathan Z. Smith est l’un des plus remarquables historiens des religions de l’ère contemporaine. En pratiquant un comparatisme inattendu entre des religions très différentes dans le temps et l’espace, cet Américain original a suscité de nouvelles manières de comprendre les mythes et les rites. A ses yeux, la religion sert à décrire des relations que des hommes entretiennent avec des acteurs surhumains dont la culture postule l’existence. En ce sens, il n’existe pas de religion pure et originelle, mais des sociétés qui reprennent à leurs comptes des représentations de mythes qui elles-mêmes en relisent de plus anciennes. Avec cet ouvrage qui reprend six articles majeurs écrits entre 1974 et 2004, le public français a enfin accès direct à Jonathan Z. Smith sur des points décisifs de sa pensée. Un entretien biographique passionnant les ponctue, dans lequel l’auteur évoque notamment le passé et l’avenir de sa discipline.

Functionalization of β-caryophyllene generates novel polypharmacology in the endocannabinoid system

The widespread dietary plant sesquiterpene hydrocarbon β-caryophyllene (1) is a CB2 cannabinoid receptor-specific agonist showing anti-inflammatory and analgesic effects in vivo. Structural insights into the pharmacophore of this hydrocarbon, which lacks functional groups other than double bonds, are missing. A structure-activity study provided evidence for the existence of a well-defined sesquiterpene hydrocarbon binding site in CB2 receptors, highlighting its exquisite sensitivity to modifications of the strained endocyclic double bond of 1. While most changes on this element were detrimental for activity, ring-opening cross metathesis of 1 with ethyl acrylate followed by amide functionalization generated a series of new monocyclic amides (11a, 11b, 11c) that not only retained the CB2 receptor functional agonism of 1 but also reversibly inhibited fatty acid amide hydrolase (FAAH), the major endocannabinoid degrading enzyme, without affecting monoacylglycerol lipase (MAGL) and α,β hydrolases 6 and 12. Intriguingly, further modification of this monocyclic scaffold generated the FAAH- and endocannabinoid substrate-specific cyclooxygenase-2 (COX-2) dual inhibitors 11e and 11f, which are probes with a novel pharmacological profile. Our study shows that by removing the conformational constraints induced by the medium-sized ring and by introducing functional groups in the sesquiterpene hydrocarbon 1, a new scaffold with pronounced polypharmacological features within the endocannabinoid system could be generated. The structural and functional repertoire of cannabimimetics and their yet poorly understood intrinsic promiscuity may be exploited to generate novel probes and ultimately more effective drugs.

Long-term live imaging reveals cytosolic immune responses of host hepatocytes against Plasmodium infection and parasite escape mechanisms

Plasmodium parasites are transmitted by Anopheles mosquitoes to the mammalian host and actively infect hepatocytes after passive transport in the bloodstream to the liver. In their target host hepatocyte, parasites reside within a parasitophorous vacuole (PV). In the present study it was shown that the parasitophorous vacuole membrane (PVM) can be targeted by autophagy marker proteins LC3, ubiquitin, and SQSTM1/p62 as well as by lysosomes in a process resembling selective autophagy. The dynamics of autophagy marker proteins in individual Plasmodium berghei-infected hepatocytes were followed by live imaging throughout the entire development of the parasite in the liver. Although the host cell very efficiently recognized the invading parasite in its vacuole, the majority of parasites survived this initial attack. Successful parasite development correlated with the gradual loss of all analyzed autophagy marker proteins and associated lysosomes from the PVM. However, other autophagic events like nonselective canonical autophagy in the host cell continued. This was indicated as LC3, although not labeling the PVM anymore, still localized to autophagosomes in the infected host cell. It appears that growing parasites even benefit from this form of nonselective host cell autophagy as an additional source of nutrients, as in host cells deficient for autophagy, parasite growth was retarded and could partly be rescued by the supply of additional amino acid in the medium. Importantly, mouse infections with P. berghei sporozoites confirmed LC3 dynamics, the positive effect of autophagy activation on parasite growth, and negative effects upon autophagy inhibition.

Structural Insight into Multivalent Galactoside Binding to Pseudomonas aeroginosa lectin LecA

Multivalent galactosides inhibiting Pseudomonas aeruginosa biofilms may help control this problematic pathogen. To understand the binding mode of tetravalent glycopeptide dendrimer GalAG2 [(Gal-β-OC6H4CO-Lys-Pro-Leu)4(Lys-Phe-Lys-Ile)2Lys-His-Ile-NH2] to its target lectin LecA, crystal structures of LecA complexes with divalent analog GalAG1 [(Gal-β-OC6H4CO-Lys-Pro-Leu)2Lys-Phe-Lys-Ile-NH2] and related glucose-triazole linked bis-galactosides 3u3 [Gal-β-O(CH2)n-(C2HN3)-4-Glc-β-(C2HN3)-[β-Glc-4-(N3HC2)]2-(CH2)n-O-β-Gal (n = 1)] and 5u3 (n = 3) were obtained, revealing a chelate bound 3u3, cross-linked 5u3, and monovalently bound GalAG1. Nevertheless, a chelate bound model better explaining their strong LecA binding and the absence of lectin aggregation was obtained by modeling for all three ligands. A model of the chelate bound GalAG2·LecA complex was also obtained rationalizing its unusually tight LecA binding (KD = 2.5 nM) and aggregation by lectin cross-linking. The very weak biofilm inhibition with divalent LecA inhibitors suggests that lectin aggregation is necessary for biofilm inhibition by GalAG2, pointing to multivalent glycoclusters as a unique opportunity to control P. aeruginosa biofilms.

The Vacuolar H+-ATPase B1 Subunit Polymorphism p.E161K Associates with Impaired Urinary Acidification in Recurrent Stone Formers

Mutations in the vacuolar–type H+-ATPase B1 subunit gene ATP6V1B1 cause autosomal–recessive distal renal tubular acidosis (dRTA). We previously identified a single-nucleotide polymorphism (SNP) in the human B1 subunit (c.481G.A; p.E161K) that causes greatly diminished pump function in vitro. To investigate the effect of this SNP on urinary acidification, we conducted a genotype-phenotype analysis of recurrent stone formers in theDallas and Bern kidney stone registries. Of 555 patients examined, 32 (5.8%) were heterozygous for the p.E161K SNP, and the remaining 523 (94.2%) carried two wild–type alleles. After adjustment for sex, age, body mass index, and dietary acid and alkali intake, p.E161K SNP carriers had a nonsignificant tendency to higher urinary pH on a random diet (6.31 versus 6.09; P=0.09). Under an instructed low–Ca and low–Na diet, urinary pH was higher in p.E161K SNP carriers (6.56 versus 6.01; P,0.01). Kidney stones of p.E161K carriers were more likely to contain calcium phosphate than stones of wild-type patients. In acute NH4Cl loading, p.E161K carriers displayed a higher trough urinary pH (5.34 versus 4.89; P=0.01) than wild-type patients. Overall, 14.6% of wild-type patients and 52.4% of p.E161K carriers were unable to acidify their urine below pH 5.3 and thus, can be considered to have incomplete dRTA. In summary, our data indicate that recurrent stone formers with the vacuolar H+-ATPase B1 subunit p.E161K SNP exhibit a urinary acidification deficit with an increased prevalence of calcium phosphate– containing kidney stones. The burden of E161K heterozygosity may be a forme fruste of dRTA.

The sensitivity and specificity of a diagnostic test of sequence-space synesthesia

People with sequence-space synesthesia (SSS) report stable visuo-spatial forms corresponding to numbers, days, and months (amongst others). This type of synesthesia has intrigued scientists for over 130 years but the lack of an agreed upon tool for assessing it has held back research on this phenomenon. The present study builds on previous tests by measuring the consistency of spatial locations that is known to discriminate controls from synesthetes. We document, for the first time, the sensitivity and specificity of such a test and suggest a diagnostic cut-off point for discriminating between the groups based on the area bounded by different placement attempts with the same item.